Potentiatied anti-tumor effectiveness of combined therapy with interleukin-12 and mitoxantrone of L1210 leukemia in vivo

In previous studies we have shown that combined chemo-immunotherapy of L121 0 leukemia with IL-12 and doxorubicin results in striking anti-tumor effect s producing 100% of long-term survivors. In this study we investigated the efficacy of a combination of IL-12 and mitoxantrone in murine L1210 leukemi a. Mice inoculated with 1x10(5) leukemia cells were treated with a single d ose of mitoxantrone and seven daily doses of IL-12, and were daily observed for survival. Treatment with IL-12 or mitoxantrone given alone produced mo derate anti-leukemic effects. However, combination of both drugs resulted i n a significant prolongation of mouse survival time. Importantly, there wer e almost 50% of long-term (>60 days) survivors among the mice treated with both agents. This therapeutic effect was completely abrogated by sub-lethal , whole-body X-irradiation, and significantly reduced after macrophage depl etion.